Discovery of Ulcer's Germ Etiology Wins Medicine Nobel

Action Points

Explain to patients that infection with H. pylori is a common cause of peptic ulcers, which means that successful treatment of ulcers requires antibiotic therapy.

STOCKHOLM, Oct. 3 - Two Australian physicians have won the 2005 Nobel Prize in Medicine or Physiology for showing - at least partly by accident -- that many ulcers are the result of a bacterial infection.

The finding by Barry Marshall, M.B., and Robin Warren, M.B., transformed the treatment of peptic ulcers, and has led to an increased understanding of the role that infection plays in several diseases.

"This is a very special prize," said Staffan Normark, M.D., Ph.D., of Sweden's Karolinska Institute, which determines each year's winner of the $1.29 million prize.

"It shows that two clinical doctors -- with very prepared minds, very determined, (but) without any particular large resources -- could make this very major discovery," Dr. Normark told reporters after the announcement.

Drs. Marshall and Warren got the news as they sat down to dinner in a Perth, Australia, restaurant. "I was shocked," the 68-year-old Dr. Warren told the Swedish News Agency TT.

"When they first rang, I did not believe it was true, that it really was the Nobel committee," he said. Then, he added, he and Dr. Marshall celebrated with beer and champagne.

Dr. Warren, who retired in 1999 from his job as a pathologist at the Royal Perth Hospital, was the first to observe curved bacteria associated with the stomach epithelium of patients with peptic ulcers.

But the prevailing wisdom of the times was that ulcers were caused by stress and lifestyle, and his findings were dismissed, even ridiculed.

Dr. Marshall, currently a researcher at the University of Western Australia, near Perth, was intrigued by Dr. Warren's work and tried unsuccessfully to grow the bacteria in the lab. Then, over the Easter holiday in 1982, a set of culture plates was left in the incubator instead of being discarded.

When Dr. Marshall returned to the lab, he found that colonies of what would later be named Helicobacter pylori. The bacteria simply grew too slowly to be found by conventional methods.

The medical establishment said that bacteria couldn't survive -- let alone cause disease -- in the acidic environment of the stomach, so the next step should have been to test the hypothesis in animals.

Unfortunately, there were no animal models of ulcers. So Dr. Marshall took the unusual step of using himself as guinea pig and drank a solution containing the newly discovered bacteria.

"I planned to give myself an ulcer, then treat myself, to prove that H. pylori can be a pathogen in normal people," he once said. It didn't result in an ulcer - but the resulting stomach inflammation was clearly surrounded by the distinctive curved bacteria.

Currently, said Dr. Normark, the medical establishment recognizes that between 80% and 90% of all peptic ulcers are due to infection by H. pylori -- an understanding that has revolutionized the treatment of the condition.

As a result of their work, treatment of gastric ulcers now includes routine testing for H. pylori followed by one of the following FDA-approved triple therapy regimens:

Lansoprazole 30 mg TID + amoxicillin 1 g TID x 2 weeks (this has restrictive labelling, it is indicated for patients who are either allergic or intolerant to Biaxin or for infections that are resistant to Biaxin) or,

Note, although not FDA approved, amoxicillin has been substituted for tetracycline for patients for whom tetracycline is not recommended.

Dr. Normark said the treatment, "has dramatically improved the lives of many people."

"Any new discovery in science is going to be controversial and initially most people won't believe it because you are going to be knocking over some kind of dogma," Dr. Marshall told reporters in Australia after the announcement.

"We were surprised that it took so long to be accepted but really for the last few years we've become vindicated," he said. "It has become mainstream treatment in Australia and in most countries."

In the years since the discovery, other researchers have investigated the role of H. pylori in stomach cancer, breast cancer, and colon cancer.

Reviewed by Robert Jasmer, MD Assistant Professor of Medicine, University of California, San Francisco

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